PROJECT SUMMARY Subthalamic deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) can be highly effective at improving motor symptoms and enhancing the patient's quality of life. However, the specific details of the anatomical target(s) for therapeutic stimulation remain unresolved. Recent DBS surgical targeting hypotheses have evolved to consider that direct stimulation of specific axonal pathways within the subthalamic region may be linked to the control of specific symptoms. Unfortunately, 3D anatomical characterization of the wide array of different axonal pathways in the human subthalamic region is very limited and techniques to visualize the complex neuroanatomy currently focus on 2D computer screens. These limitations hinder our ability to create accurate models and interpret the effects of DBS. Therefore, we propose that significant need exists for an anatomically driven model of subthalamic axonal pathways that can be interactively visualized with holographic 3D imaging and coupled to patient-specific DBS simulations. The goal of this Bioengineering Research Grant (PAR-16-242) is to create next generation visualization tools and surgical targeting models for clinical DBS. The first step of this study will rely on direct input from a collection of world experts in basal ganglia neuroanatomy to help us build a virtual 3D atlas model of 8 different axonal pathways in the subthalamic region. This development will occur within the HoloLens augmented reality (AR) environment, thereby enabling face-to-face discussion among the anatomy experts while visualizing the model hologram and its interactive adjustment. The second step of this study will evaluate the ability of various tractography algorithms to recreate the pathways described by the anatomy experts. We hypothesize that tractography will fail to accurately capture the anatomical trajectory of most subthalamic axonal pathways without extensive modeling constraints. Results from this analysis will have important implications for the rapid growth of tractography in DBS research, as well as clinical practice. Finally, we will translate our subthalamic axonal pathway model system into an interactive HoloLens AR application that works in concert with patient-specific MRI datasets and DBS pathway-activation modeling. We propose that such a tool will be especially useful for DBS surgical education and research investigation.